Work

Characterizing HIV expression of proviruses during ART in tissues and blood

Year: 2017

Type: article

Abstract: Background: HIV proviruses persist during ART in latent and transcriptionally-active forms.Little is known regarding the fraction of infected cells in blood and in tissues that are quiescent versus those that actively express unspliced HIV-1 RNA in either the total population of infected cells or in infected cell clones.The fraction of cells that actively transcribe HIV-1 RNA during ART may be associated with the time to viral rebound if ART is interrupted and/or to the rate of spontaneous reactivation of latently-infected cells.Methods: PBMC and LNMC were obtained from five donors: four had <40 cps/ml on ART for 4.3-12.9years and one was ART-naïve.Proviral populations and their expression were characterized by cell associated RNA-and DNA-single genome sequencing of p6-PR-RT to determine the fraction of infected cells with transcriptionally-silent proviruses and the fraction with proviruses that were undergoing transcription in vivo at the time of sample collection.Results: The number of infected cells in the PBMC and LNMC was not different during full suppression on ART, especially when normalized for the total number of CD4+ T cells in each compartment (p=0.9).Transcriptionally-active proviruses, including those in probable cell clones, were found in both LNMC and PBMC.However, a greater fraction of infected cells in LNMC contained unspliced HIV RNA both before and during ART than in PBMC (mean 13% vs. 6%, p=0.01).High-expressing cells (>20 HIV RNA copies/cell) were observed in the untreated individual but not in samples collected on ART, with the exception of one LNMC.Conclusions: Greater than 80% of HIV proviruses in vivo are transcriptionally-silent after long-term suppression of viremia on ART.However, a higher fraction of infected cells in the lymph nodes have transcriptionally-active proviruses during ART than in the peripheral blood.Profiling HIV proviral expression during ART will lead to a better understanding of the HIV reservoir, the nature of latency, and the sources of rebound viremia when ART is interrupted.

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30539-2